search
Back to results

Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia

Primary Purpose

Post Bariatric Hypoglycemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lyo avexitide
Liq avexitide
Sponsored by
Tracey McLaughlin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post Bariatric Hypoglycemia focused on measuring Bariatric surgery complications, Glucose Metabolism Disorders, Exendin (9-39), GLP-1

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Post-bariatric surgery more than 6 months prior to signing the informed consent
  • Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms associated with a capillary blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration.
  • Symptomatic hypoglycemia during the baseline/screening oral glucose tolerance test (OGTT), as defined by the presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic symptoms.

Exclusion Criteria:

  • Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug.
  • Participation in any clinical investigation within 4 weeks prior to dosing
  • History of or current insulinoma
  • Active infection or significant acute illness within 2 weeks prior to dosing
  • Female patients who are pregnant or lactating
  • Women of childbearing potential and not utilizing effective contraceptive methods
  • Inadequate end organ function

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part A: Lyo avexitide 0.05 mg/kg

Part A: Lyo avexitide 0.15 mg/kg

Part A: Lyo avexitide 0.35 mg/kg

Part A: Lyo avexitide 0.46 mg/kg

Part B: Liq avexitide 0.38 (±0.03) mg/kg

Arm Description

Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days

Participants will receive Lyo avexitide twice daily for 3 days

Participants will receive Lyo avexitide twice daily for 3 days

Participants will receive Lyo avexitide twice daily for 3 days

Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days

Outcomes

Primary Outcome Measures

Nadir Glucose
Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).

Secondary Outcome Measures

Change in Composite Symptom Score as a Measure of Treatment Effect
Symptoms of hypoglycemia were assessed using the Edinburgh Hypoglycemia Symptom Scale that measures the intensity of 13 commonly experienced hypoglycemic symptoms, each severity graded on a 6-point Likert scale (0 = not present, 5 = severe). Scores are summed for a composite score ranging from 0 to 65, with higher scores corresponding to more severe hypoglycemia symptoms.
Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.

Full Information

First Posted
May 6, 2016
Last Updated
October 19, 2020
Sponsor
Tracey McLaughlin
Collaborators
Eiger BioPharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT02771574
Brief Title
Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia
Official Title
A Phase 2 Multi-Ascending Dose Trial to Assess the Efficacy, Tolerability and Pharmacokinetic Profile of Exendin (9-39) in Patients With Post-bariatric Hyperinsulinemic Hypoglycemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Tracey McLaughlin
Collaborators
Eiger BioPharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is designed to evaluate the efficacy, safety and pharmacokinetics of subcutaneous exendin (9-39) in subjects with post-bariatric hypoglycemia. Development of this subcutaneous formulation of exendin (9-39) would represent a targeted therapeutic approach for this rare disease with unmet clinical need.
Detailed Description
Post-Bariatric Hypoglycemia (PBH) is a rare, but increasingly reported disease occurring after bariatric surgery, characterized by severe hypoglycemic episodes accompanied by symptoms of hypoglycemia. At the moment, no medical therapies have been developed for this disorder, but the clinical need is great. The major contributory factor is thought to be an exaggerated secretion of glucagon-like peptide-1 (GLP-1) due to altered nutrient transit after bariatric surgery. GLP-1 is an incretin hormone secreted primarily by the distal ileum that contributes to postprandial glucose regulation. Exendin (9-39) is a specific GLP-1 receptor antagonist, that when given via continuous IV infusion, has been shown to effectively prevent postprandial hypoglycemia and reduce symptoms of hypoglycemia in patients with PBH. This study is designed to assess the efficacy, safety and pharmacokinetic profile of a novel subcutaneous formulation of exendin (9-39).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Bariatric Hypoglycemia
Keywords
Bariatric surgery complications, Glucose Metabolism Disorders, Exendin (9-39), GLP-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare Provider
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A: Lyo avexitide 0.05 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days
Arm Title
Part A: Lyo avexitide 0.15 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive Lyo avexitide twice daily for 3 days
Arm Title
Part A: Lyo avexitide 0.35 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive Lyo avexitide twice daily for 3 days
Arm Title
Part A: Lyo avexitide 0.46 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive Lyo avexitide twice daily for 3 days
Arm Title
Part B: Liq avexitide 0.38 (±0.03) mg/kg
Arm Type
Experimental
Arm Description
Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days
Intervention Type
Drug
Intervention Name(s)
Lyo avexitide
Other Intervention Name(s)
Exendin (9-39)
Intervention Description
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
Intervention Type
Drug
Intervention Name(s)
Liq avexitide
Other Intervention Name(s)
Exendin (9-39)
Intervention Description
Liquid avexitide (Liq avexitide) administered subcutaneously (sc)
Primary Outcome Measure Information:
Title
Nadir Glucose
Description
Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).
Time Frame
Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Secondary Outcome Measure Information:
Title
Change in Composite Symptom Score as a Measure of Treatment Effect
Description
Symptoms of hypoglycemia were assessed using the Edinburgh Hypoglycemia Symptom Scale that measures the intensity of 13 commonly experienced hypoglycemic symptoms, each severity graded on a 6-point Likert scale (0 = not present, 5 = severe). Scores are summed for a composite score ranging from 0 to 65, with higher scores corresponding to more severe hypoglycemia symptoms.
Time Frame
Baseline, Day 3
Title
Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)
Description
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Time Frame
Day 3 (Predose)
Title
Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)
Description
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Time Frame
Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Title
Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax)
Description
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Time Frame
Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Title
Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC)
Description
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Time Frame
Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Post-bariatric surgery more than 6 months prior to signing the informed consent Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms associated with a capillary blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration. Symptomatic hypoglycemia during the baseline/screening oral glucose tolerance test (OGTT), as defined by the presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic symptoms. Exclusion Criteria: Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug. Participation in any clinical investigation within 4 weeks prior to dosing History of or current insulinoma Active infection or significant acute illness within 2 weeks prior to dosing Female patients who are pregnant or lactating Women of childbearing potential and not utilizing effective contraceptive methods Inadequate end organ function
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marilyn Tan, MD
Organizational Affiliation
Clinical Assistant Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32250530
Citation
Tan M, Lamendola C, Luong R, McLaughlin T, Craig C. Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. Diabetes Obes Metab. 2020 Aug;22(8):1406-1416. doi: 10.1111/dom.14048. Epub 2020 May 4.
Results Reference
result

Learn more about this trial

Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia

We'll reach out to this number within 24 hrs